Arteriovenous (AV) fistula non-maturation is currently a huge clinical problem and a major cause of morbidity and increased costs in the hemodialysis population. Although AV fistulae are the preferred mode of dialysis access they have a very high incidence of maturation failure due to a juxta-anastomotic venous stenosis. This results in multiple endovascular and surgical procedures, together with prolonged catheter dependence (the latter often resulting in sepsis). Despite the magnitude of the clinical problem, however, we currently nave no way of predicting which patients are at high risk of AV fistula non-maturation. The central objective of the current proposal is to identify predictive markers for AV fistula success or failure. In the longer term, we believe that the mechanistic information obtained from this work, will allow for the development of novel therapies to enhance AV fistula maturation. We plan to address our central objective through a prospective, cohort, observational study which will enroll upto 1200 patients who require a new AV fistula over 6-8 clinical sites. In Specific Aim 1, we will assess the impact of clinical markers such as demographics, co-morbidities, vessel size and previous vascular access history on AV fistula maturation and patency. In Specific Aim 2, we will study the relationship between hemodynamic markers such as blood flow, physical examination, the angle of the AV anastomosis and hemodynamic shear stress on AV fistula maturation. Finally, in Specific Aim 3, we will examine the role of biological markers such as oxidative stress and endothelial function on AV fistula maturation. Logistic regression analyses will be performed to identify both individual predictors and groups of predictors for AV fistula non-maturation. We will also use this data to develop clinician friendly risk scores for use both prior to surgery and after AV fistula placement. We believe that the current proposal will allow us to stratify patients requiring a new dialysis access into high and low risk groups. Patients in the high risk group would then either be targeted for aggressive follow up and intervention or considered for alternate forms of dialysis access (PTFE grafts). Looking to the future, we also hope that the mechanistic information obtained from this study will allow us to develop novel therapeutic interventions to enhance AV fistula maturation. This could reduce the huge clinical and economic burden currently associated with AV fistula non-maturation. Relevance to Public Health: A better understanding of the factors responsible for AV fistula stenosis could allow us to develop better ways of predicting, monitoring and treating all forms of vascular stenosis including coronary, carotid and peripheral vascular disease.